COW-2021-30

1. c; 2. b

Biphasic papillary renal cell carcinoma (BPRCC)

Biphasic papillary renal cell carcinoma (BPRCC) is a variant of papillary renal cell carcinoma first described in 2012 and not currently on the WHO classification. Other synonyms include biphasic alveolosquamoid renal carcinoma, and biphasic squamoid alveolar renal cell carcinoma due to the dual or biphasic cell population.

The tumor is grossly white to tan brown and frequently multifocal. Microscopically, it is solid compact with small cystic areas. There is a characteristic biphasic morphology with two-cell population, a larger eosinophilic “squamoid” cells with abundant cytoplasm and higher-grade nuclei surrounded or admixed with a smaller cell population of cuboidal and amphophilic cells with scanty cytoplasm. Psammoma bodies and macrophages are also present. There is no evidence of keratin pearls or true squamous phenotype, with negative CK5/6 and P63, hence the designation of “squamoid” cells.

The squamoid cell clusters have a characteristic alveolar, glomeruloid or micronodular architecture with cytophagocytosis (reported as emperipolesis) of apoptotic neutrophilic granulocytes, cell fragments, and debris. They are negative for the squamous markers CK5/6 and p63; and exclusively positive for cyclin-D1 (BCL-1) and, while the smaller cells surround the clusters are negative. In our case, the squamoids cells were also exclusively positive for high molecular weight keratin (CK-903). CD57 expression has also been reported limited to the squamoid cells. There is an opposite staining pattern with RCC in this case, where RCC is limited to the smaller cells (image 5).

BPRCC is uniformly positive for EMA, CAM5.2, pancytokeratin, alpha methyl Co-A racemase, and PAX8; variable positive for CD10 and 34βE12 (CK-903); and negative for carbonic anhydrase 9, CD117, GATA-3, WT1, CK5/6, and CK20, vimentin, parvalbumin, S100 protein, S100 A1, p63, p53, CDX2, uroplakin III, HMB45, TFE3, WT1, synaptophysin, chromogranin A, thyroglobulin, and TTF1. The Ki67 proliferation index has been reported higher on the squamoid cells (more than 5% up to 25%). Ultrastructurally, the squamoid cells have desmosomes and tonofilaments.

BPRCC can be bilateral, multifocal and associated with papillary adenomas, other papillary RCCs, clear cell RCC, and low-grade urothelial carcinoma.

The genetic profile can be similar to other papillary RCCs with gain of chromosome 7 and 17 and loss of chromosome Y, as well as multiple chromosomal aberrations in regions of known tumor suppressor genes and oncogenes. MET alterations support BPRCC as a morphological variant of type 1 papillary RCC.

The survival data is limited since BPRCC is a newly described entity, with a series reporting metastatic disease in 24% of the cases; and metastasis, recurrence, or death due to the disease in 15% of patients.

The differential diagnosis includes papillary renal cell carcinoma, type 2 and oncocytic variant (Cyclin D1-); metanephric adenoma (option e. WT1 +, CD57+, alpha methyl Co-A racemase -, EMA -, CK7 -); urothelial carcinoma with squamous differentiation (option c. P63 +, GATA3 +, uroplakin +, PAX8 -, high molecular weight keratin +); chromophobe renal cell carcinoma with squamous differentiation (option d. vimentin –, CD117 +, e-cadherin +, CK7 +, hales colloidal iron +); alveolar soft part sarcoma (option a. TFE3 +, MyoD1 +, PAS + diastase resistant); and mucinous tubular and spindle cell carcinoma (PAX8 +, EMA +, CK-903, stroma + for alcian blue, NSE, synaptophysin, chromogranina, PSA).

Biphasic papillary renal cell carcinoma is a rare variant of papillary renal cell carcinoma with squamoid cyclin-D1 (BCL-1) positive cells, multifocality, small tumor size, and indolent but potentially aggressive behavior.

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5. Trpkov K, Athanazio D, Magi-Galluzzi C, Yilmaz H, Clouston D, Agaimy A, Williamson SR, Brimo F, Lopez JI, Ulamec M, Rioux-Leclercq N, Kassem M, Gupta N, Hartmann A, Leroy X, Bashir SA, Yilmaz A, Hes O. Biphasic papillary renal cell carcinoma is a rare morphological variant with frequent multifocality: a study of 28 cases. Histopathology. 2018 Apr;72(5):777-785. PMID: 29119638

6. Biphasic squamoid alveolar renal carcinoma with positive CD57 expression: A clinicopathologic study of three cases. Zhou L, Xu H, Zhou Y, Zhou J, Zhang P, Yang X, Wang C. Pathol Int. 2019 Sep;69(9):519-525. PMID: 31369187 Review.

7. Denize T, Just PA, Sibony M, Blons H, Timsit MO, Drossart T, Jakubowicz D, Broudin C, Morini A, Molina T, Vano Y, Auvray-Kuentz M, Richard S, Mejean A, Gimenez Roqueplo AP, Burnichon N, Verkarre V. MET alterations in biphasic squamoid alveolar papillary renal cell carcinomas and clinicopathological features. Mod Pathol. 2021 Mar;34(3):647-659. PMID: 32770124

8. Cimadamore A, Cheng L, Scarpelli M, Massari F, Mollica V, Santoni M, Lopez-Beltran A, Montironi R, Moch H. Towards a new WHO classification of renal cell tumor: what the clinician needs to know—a narrative review. Transl Androl Urol 2021;10(3):1506-1520. doi: 10.21037/tau-20-1150

9. Suárez-Vilela D, Izquierdo FM, Méndez-Álvarez JR, Velasco-Alonso J. The Squamoid Cells in Biphasic Squamoid Alveolar Renal Carcinoma Present Cytophagocytosis (Not Emperipolesis) of Apoptotic Neutrophilic Granulocytes. Am J Surg Pathol. 2018 Mar;42(3):420-422. PMID: 29194094

Ruth Birbe; William Rafferty
Cooper University Hospital-MD Anderson Cancer Center
USA

Kidney

kidney; Biphasic squamoid papillary RCC; cyclin-D1; BCL-1